BsYetJ is a bacterial homolog of transmembrane BAX inhibitor-1 motif-containing 6 (TMBIM6) membrane protein that plays a key role in the control of calcium homeostasis. However, the BsYetJ (or TMBIM6) structure embedded in a lipid bilayer is uncharacterized, let alone the molecular mechanism of the calcium transport activity. Herein, we report structures of BsYetJ in lipid nanodiscs identified by double electron–electron resonance spectroscopy. Our results reveal that BsYetJ in lipid nanodiscs is structurally different from those crystallized in detergents. We show that BsYetJ conformation is pH-sensitive in apo state (lacking calcium), whereas in a calcium-containing solution it is stuck in an intermediate, inert to pH changes. Only when the transmembrane calcium gradient is established can the calcium-release activity of holo-BsYetJ occur and be mediated by pH-dependent conformational changes, suggesting a dual gating mechanism. Conformational substates involved in the process and a key residue D171 relevant to the gating of calcium are identified. Our study suggests that BsYetJ/TMBIM6 is a pH-dependent, voltage-gated calcium channel.

This work reports cascade cyclization between 1allenyl-2-alkynylbenzenes and nitrosoarenes. When these two components reacted alone under N 2 , N,O-functionalized indanefused isoxazolidines 3 were obtained selectively. DFT calculations verify that this reaction sequence involves unprecedented nitrone/ alkyne cycloadditions, followed by diradical rearrangement.

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The transmembrane BAX inhibitor-1-containing motif 6 (TMBIM6) is an anti-apoptotic endoplasmic reticulum (ER) membrane protein. The suppression of apoptosis by TMBIM6 is linked to its role in regulating calcium homeostasis. However, the molecular mechanisms underlying the calcium regulation in the ER remain poorly understood. Using mutagenesis and fluorescence-based functional assays, this study investigates all the highly conserved negatively charged residues in the BsYetJ (a bacterial homolog of TMBIM6) and reveals that the charged residues E49 and R205 cooperatively act as a major calcium-selectivity filter determining the channel conductance. This study identifies the conformations of BsYetJ in the ER environment using electron spin resonance and molecular dynamics. Together with the functional data, we propose a mechanism, composed of two selectivity filters, for the calcium-dependent inactivation of BsYetJ observed in the ER environment. Overall, this study provides a framework for understanding the non-canonical calcium gated membrane protein, which will facilitate structure-based development of more effective medications for TMBIM6.

This study aims to investigate how two NNES (non-native English speaking) Taiwanese engineering graduate students became enculturated through various disciplinary practices of their disciplines. In particular, it focused on the learning challenges they had encountered during their overall process of disciplinary enculturation through the lens of legitimate peripheral participation. This study was conducted for the fall semester over the academic year of 2017 and 2018 at two universities in Taiwan. Multiple sources of data such as transcripts of student interviews, writing samples, and lab observations were collected and analysed. The findings indicated that the overall English proficiency of these students played a crucial role in their overall process of disciplinary enculturation. In addition, both students longed for more guidance from their disciplinary mentors/instructors regarding how to present their research and write for journal papers more effectively in English. Moreover, participants encountered varying degrees of writing challenges in writing for scholarly publications. The findings supported previous studies that NNES students often struggled most with various linguistic challenges relevant to their English language proficiency and they needed more guidance from advisors to facilitate their acquisition of genres in their target discipline.